Sugammadex sodium (abbreviated as SGMD) was first discovered by Organon Biosciences. In 2007, Organon Biosciences was acquired by Schering-Plough, the latter merged with Merck & Co. in 2009. SGMD is now owned and sold by Merck & Co. SGMD and its injection were approved by EMEA at the end of 2009, of which the tradename is Bridion. In 2010, SGMD was approved by PMDA and then by FDA in December 2015. Since then, SGMD and its injection have been launched in more than 50 countries all over the world. In 2015, CFDA approved the application of SGMD injection as investigational new drug (IND) by N.V. Organon's.
Sugammadex sodium represents the first and only selective relaxant binding agent (SRBA) and is one of the most notable achievements in the field of anaesthetic during the last 20 years. SGMD chelates free rocuronium bromide molecules thus rapidly reduces the concentration thereof in plasma. The transfer of rocuronium bromide molecule from neuromuscular junction to plasma caused by the concentration difference between them renders in the decrease of the concentration of rocuronium bromide molecule at neuromuscular junction so that rocuronium bromide molecule bound to nicotinic acetylcholine receptors (nAChRs) is released at neuromuscular junction which results in the reversal of neuromuscular blockade induced by rocuronium bromide molecule.
Sugammadex sodium binds to and inactivates non-polarizing muscle relaxants with high selectivity. It antagonizes rocuronium bromide molecule due to the chelating between the lipophilic core of SGMD and the rocuronium bromide molecules. The similar antagonism works also to vecuronium bromide which is an analogue of rocuronium bromide molecule. However, no reversal effect for neither the non-depolarizing muscle relaxants with the structure of benzyl isoqunoline e.g., cis-atracurium, nor the depolarizing neuromulscular blocking agents e.g., succinylcholine.
Sugammadex sodium is a modified derivative of γ-cyclodextrin which contains 8 glucopyranose units with a lipophilic core and a hydrophilic periphery. The full chemical name of SGMD is 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin, sodium salt. Its structure is shown as below:

Due to its complex structure, extreme polarity and good water solubility, the preparation and purification of SGMD becomes very difficult since the impurities produced during the preparation thereof have physico-chemical characteristics and molecular weights comparable to that of the active substance. The current existing methods for the preparation of SGMD are as listed as follows:
1. Patent CN1188428C (cognate patent of EP1259550B1) assigned to Akzo Noble, the inventor of Sugammadex sodium.
The process described in this patent started from γ-cyclodextrin, which reacts with iodine and triphenylphosphine to afford an intermediate, 6-per-deoxy-6-iodo-γ-cyclodextrin (SGMD-1). The intermediate SGMD-1 thus prepared reacts with 3-mercaptopropionic acid to provide the crude Sugammadex sodium salt by nucleophilic substitution which was further purified by passing through macroporous resin and dialysis to remove impurities. The preparation of SGMD-1 according to this process requires cooling the reaction system prior to the addition of sodium methoxide and mixing the mixture prior to the addition of methanol and evaporation thereof.
2. Patents WO2012025937 and WO2014125501.
Compared to the route described in the patent CN1188428C, the process in this patent (WO2014125501) employed a different intermediate rather than SGMD-1. γ-cyclodextrin reacts with phosphorous pentachloride (or phosphorous pentabromide) instead of iodine and triphenylphosphine to afford 6-per-deoxy-6-chloro (or bromo)-γ-cyclodextrin which reacts with 3-mercaptopropionic acid by nucleophilic substitution to afford the crude SGMD which is further purified to obtain SGMD.
The preparation of SGMD described in patent WO2012025937 was same to that in patent WO2014125501, both of them use phosphorous pentahalide instead of iodine and triphenylphosphine used in CN1188428C. This process requires also the evaporation of DMF, a high boiling point organic solvent, at the end of the first step. In the second step, the addition of ethanol to the reaction system will precipitate the product of SGMD as well as the unreacted SGMD-1. Thus the purification requires silica gel and sephadex G25 column chromatography. While in patent WO2014125501, the crude SGMD was purified by recrystallization with methanol, ethanol, acetonitrile and water. Prior to recrystallization, active carbon was added to decolorize the product.